Channel-Water Dynamics are Correlated with the Conformational Changes of the M2 Viroporin Protein from Influenza a Virus

Abstract

Viroporins are a class of viral ion channels that are involved in diverse processes entry, assembly and virulence. In the pursuit of understanding the mechanism of viroporins, knowledge of both structural and dynamic characteristics is essential. An experimental technique, sensitive to both structure and dynamics of the viroporin, is ideal for serving the purpose. Here, using the structure-sensitive two-dimensional infrared (2D IR) spectroscopy, with ultrafast time resolution, we have shown a direct correlation between channel-water dynamics and the conformational changes of the M2 viroporin from influenza A virus inserted into a solid-supported lipid bilayer. Our results show that a helix kink at higher pH (7.5) occludes the passage of water molecules into the channel, making it inactive. The stretched M2 structure at low pH (5.5) shows ultrafast hydrogen-bond dynamics between the backbone amide carbonyls and the water molecules, confirming the presence of water inside the channel in its active state. These results provide direct experimental evidence for a transporter-likeconduction mechanism, relating the channel-water dynamics with domain-specific structural changes in the viroporin. The results indicate that such experiments can be exploited for other topical coronaviruses (CoVs) viroporins, warranting investigation.